It is now well established that cellular interactions are at least in part mediated by receptor/ligand interactions. One class of receptors is known to recognize the peptide subsequence "RGD"; other receptors recognize carbohydrate ligands.
One class of receptors that recognize carbohydrate-based ligands mediates the adhesion of circulating neutrophils to stimulated vascular endothelium. This is a primary event of the inflammatory response and appears to be involved as well in allergic and autoimmune responses. Several of the lectin-based receptors that are presumably involved in this process include LECAM-1 (gp90.sup.mel); gmp-140 (PADGEM) and ELAM-1 (LECAM-2). Of particular interest herein is the ELAM-1 receptor which has been shown to interact with the sialyl-Lewis.sup.x oligosaccharide (NeuAc(.alpha.2,3)Gal(.beta.1,4)[Fuc (.alpha.1,3)]GlcNAc.
U.S. patent application Ser. No. 07/683,458, filed Apr. 11, 1991, now U.S. Pat. No. 5,211,937 assigned to the present assignee and incorporated herein by reference discloses and claims the foregoing minimum tetrasaccharide structure and identifies the groups putatively interactive with the ELAM-1 receptor.
The present invention provides analogs of the sialyl-Lewis.sup.x residue which are agonists or antagonists of the ELAM-1 receptor and related cell adhesion receptors as well as an improved synthetic method to prepare both these analogs and compounds which are derivatives of lactose or lactosamine in general.